NMR paper Ranking high affinity ligands of low solubility by NMR spectroscopy.

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[NMR paper] Ranking high affinity ligands of low solubility by NMR spectroscopy.

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NMR processing:

MDD

NMR assignment:

Backbone:

Side-chains:

NOEs:

Structure from NMR restraints:

Ab initio:

Fragment-based:

Rosetta-NMR (Robetta)

Template-based:

GeNMR

I-TASSER

Refinement:

Amber

Structure from chemical shifts:

Fragment-based:

Homology-based:

Torsion angles from chemical shifts:

Preditor

TALOS

Promega- Proline

Secondary structure from chemical shifts:

CSI (via RCI server)

TALOS

MICS caps, β-turns

d2D

PECAN

Flexibility from chemical shifts:

RCI

Interactions from chemical shifts:

HADDOCK

Chemical shifts re-referencing:

NMR model quality:

NOEs, other restraints:

Chemical shifts:

RDCs:

Pseudocontact shifts:

Protein geomtery:

SAVES2 or SAVES4

Quality Control Check

NMR spectrum prediction:

FANDAS

MestReS

V-NMR

Flexibility from structure:

Backbone S2

Methyl S2

B-factor

Molecular dynamics:

Gromacs

Amber

Antechamber

Chemical shifts prediction:

From structure:

Shiftx2

Sparta+

Camshift

CH3shift- Methyl

ArShift- Aromatic

ShiftS

Proshift

PPM

CheShift-2- Cα

From sequence:

Shifty

Camcoil

Poulsen_rc_CS

Disordered proteins:

MAXOCC

Format conversion & validation:

CCPN

From NMR-STAR 3.1

Validate NMR-STAR 3.1

NMR sample preparation:

Protein disorder:

DisMeta

Protein solubility:

Isotope labeling:

Solid-state NMR:

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06-07-2014, 07:12 PM

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Ranking high affinity ligands of low solubility by NMR spectroscopy.

Ranking high affinity ligands of low solubility by NMR spectroscopy.

Related Articles Ranking high affinity ligands of low solubility by NMR spectroscopy.

ACS Med Chem Lett. 2011 Jun 9;2(6):485-7

Authors: Landrieu I, Hanoulle X, Fritzinger B, Horvath D, Wieruszeski JM, Lippens G

Abstract
Cyclosporine A (CsA) and its chemical analogues EthVal4Cs, MeVal4Cs, and Me(d-Ala)3EthVal4Cs (Alisporivir) all interact with cyclophilin A (CypA). The latter Alisporivir is a nonimmunosuppressive CsA derivative that has potent anti-HCV properties in clinical trials. We show here that NMR spectroscopy can be used to rank this series of related pharmacological molecules despite their high affinity for the target protein and low solubility in water. The novel method is based on the possibility to detect distinct NMR signals from the different protein complexes in a mixture. The method has enabled us to distinguish subtle effects of discrete chemical modifications of the parent molecule on the affinity of the ligands for the target protein.

PMID: 24900335 [PubMed]

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